Navigation Links
Brain cell migration during normal development may offer insight on how cancer cells spread
Date:4/24/2011

SEATTLE By shedding new light on how cells migrate in the developing brain, researchers at Fred Hutchinson Cancer Research Center also may have found a new mechanism by which other types of cells, including cancer cells, travel within the body. The findings by Jonathan Cooper, Ph.D., member and director of the Hutchinson Center's Basic Sciences Division, and Yves Jossin, Ph.D., a research fellow in Cooper's laboratory, published online April 24 in Nature Neuroscience, could lead to a better understanding of neurological development and, possibly, cancer metastasis.

During normal development cells divide, arrange themselves in appropriate patterns, and specialize to form discrete tissues and organs. For the body to develop properly, cells must coordinate their migratory patterns and the process by which they differentiate, or evolve from less-specialized cells into more-specialized cell types. A lack of such coordination leads to disordered development and, in some cases, cancer.

Jossin and Cooper set out to analyze how cells migrate in the cerebral cortex of the developing brain. The cerebral cortex, gray matter of the cerebrum, is the brain's command and control center where cognition and planning occur, and it is particularly well developed in humans.

The cerebral cortex is composed of horizontal layers of nerve cells, or neurons, which are specialized for different functions and connected vertically into circuits. If some neurons are in the wrong layers, the wiring can be defective and neurological disorders including epilepsy, autism and schizophrenia may result.

In the fetus, the cortex grows "from the inside out" via the sequential addition of new neurons, which move from the inside, pass between neurons in previously established intermediate layers, and form new layers on the outside. How the migrations are regulated remains unclear despite years of study.

Jossin and Cooper now report the discovery of signals that control a particular stage in a cortical neuron's journey. New neurons initially move in a straight line, from the inside to the outside, until they reach a layer called the intermediate zone. This zone contains relatively few neurons but many connecting fibers, or axons. When new neurons reach this layer, they lose their way and start wandering up, down, left and right, frequently changing direction. When, seemingly by chance, they emerge from the intermediate zone, they realign with their original direction of movement and speed ahead through layers of differentiated neurons towards the outer surface of the cortex.

The researchers aimed to determine how neurons get back on track after they emerge from the chaos of the intermediate zone. They identified a signaling protein, called Reelin, which is made by cells in the outermost layer of the cortex. It has been known for years that mutations in the Reelin gene cause profound cortical layering abnormalities in rodents and people, but it has been unclear which stage of neuron migration goes awry when Reelin is absent.

The new study shows that new neurons respond to Reelin as they emerge from the intermediate zone. "This is remarkable because the top layer of the cortex, where Reelin is made, is widely separated from the top of the intermediate zone, where it acts, so the Reelin protein must be diffuse," Cooper said. "It is also remarkable that Reelin seems not to be a direction signal itself. Rather, Reelin triggers changes in the membranes of the migrating neurons that allow the cells to respond to direction signals."

The researchers show that a membrane protein called N-cadherin increases on the surface of neurons when the neurons encounter Reelin. The surface increase in N-cadherin allows the cell to choose the appropriate direction for its next stage of migration. "This represents a new and surprising function for N-cadherin," Jossin said, "because normally this protein acts as a cellular stabilizer and not as an orchestrator of migration."

For example, elsewhere in the cortex, N-cadherin forms tight adhesions between adjacent cells and prevents them from moving. Indeed, the general role for cadherins in the body is to stabilize sheets of cells and organize tissues by holding cells together.

"The new role for N-cadherin in orienting migrating cells is quite unexpected and suggests that cadherins on the surface of other types of normal or cancer cells may also be involved in helping them move rather than stay in place," Jossin said. "This finding could provide new clues to how normal and cancerous cells migrate within the body," he said.


'/>"/>

Contact: Kristen Woodward
kwoodwar@fhcrc.org
206-667-5095
Fred Hutchinson Cancer Research Center
Source:Eurekalert

Related biology news :

1. USC research shows critical role of placenta in brain development
2. Evolution of human super-brain tied to development of bipedalism, tool-making
3. Toward new medications for chronic brain diseases
4. FDA approves the NovoTTF-100A system for the treatment of patients with recurrent glioblastoma multiforme (GBM) brain tumors
5. Giant fire-bellied toads brain brims with powerful germ-fighters
6. Allen Institute for Brain Science announces first comprehensive gene map of the human brain
7. Alcohol helps the brain remember, says new study
8. Mapping the brain: New technique poised to untangle the complexity of the brain
9. Dopamine controls formation of new brain cells
10. People control thoughts better when they see their brain activity: UBC study
11. Freeway air bad for mouse brain
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/21/2016)... , January 21, 2016 ... a new market research report "Emotion Detection and Recognition ... Software Tools (Facial Expression, Voice Recognition and Others), ... Global forecast to 2020", published by MarketsandMarkets, the ... to reach USD 22.65 Billion by 2020, at ...
(Date:1/18/2016)... Calif. , Jan. 18, 2016  Extenua ... software that simplifies the use and access of ... and go-to-market partnership with American Cyber.  ... brings extensive experience leading transformational C4ISR and Cyber ... and integrating the latest proven technology solutions," said ...
(Date:1/11/2016)... , Jan. 11, 2016 Synaptics Incorporated (NASDAQ: ... solutions, today announced that its ClearPad ® TouchView ... products won two separate categories in the 8 th ... and Best Technology Breakthrough. The Synaptics ® TDDI ... simplified supply chain, thinner devices, brighter displays and borderless ...
Breaking Biology News(10 mins):
(Date:2/11/2016)... Feb. 11, 2016  Wellcentive today announced it ... Portland, Oregon -based community care organization (CCO) ... health analytics, quality reporting and care management solutions ... its team of quality managers, analysts and care ... provider groups serving FamilyCare members. ...
(Date:2/11/2016)... BEACH, Florida , February 11, 2016 /PRNewswire/ ... PositiveID Corporation ("PositiveID" or "Company") (OTCQB: PSID), ... diagnostics, announced today that its Thermomedics subsidiary, which ... progress on its growth plan in January 2016, ... products distributors, increasing sequential monthly sales growth, and ...
(Date:2/11/2016)... ... , ... Global Stem Cells Group, a world ... Cells Network (GSCN) to distribute exosome injection and other biological products to stem ... Dominican Republic, Colombia, Argentina, Nicaragua, Panama, El Salvador, Venezuela, Peru, Ecuador, Paraguay, Puerto ...
(Date:2/10/2016)... Early-career researchers from Indonesia ... Uganda and Yemen ... Indonesia , Nepal , ... Yemen are being honored for their accomplishments in nutrition, psychiatry, ... mentoring young women scientists who are pursuing careers in agriculture, biology and ...
Breaking Biology Technology: